UCI study helps identify one reason why women have lower stroke risk than men

Estrogen's role as an inhibitor of toxic-free radicals in cerebral blood vessels may be a key reason why premenopausal women have a lower stroke risk than men.

According to UC Irvine School of Medicine researchers, estrogen has a powerful and positive influence on women’s health by increasing the energy production efficiency of mitochondria – the tiny power plants that provide cells the energy they need to function. And in doing so, the hormone inhibits the mitochondrial production of free radical oxygen molecules. Previous studies have shown that excessive amounts of these radical elements in the body, through a process called oxidative stress, can damage blood vessels and lead to stroke or degenerative disease.

In the UCI study, Dr. Vincent Procaccio of the Center for Molecular and Mitochondrial Medicine and Genetics and colleagues discovered estrogen receptors in vascular mitochondrial cells. To see how mitochondria functioned with deficient estrogen levels, they removed the ovaries from test rats, which suppressed any hormone influence, and identified a significant increase in radical oxygen molecule levels and a decline in the capacity for mitochondria to produce energy. In rats treated with doses of estrogen, however, vascular mitochondria produced energy more efficiently with lower amounts of damaging free radicals.

“We want to find out more how estrogen can protect blood vessels in the brain,” said Procaccio, also an assistant professor of pediatrics. “And when we gain a fuller understanding, we hopefully can figure out how best to realize potential benefits of hormone replacement therapies. Also, learning the mechanisms by which estrogen is beneficial to brain circulation may give us new ideas about how to protect against stroke.”

Spurred by recent findings of the Women’s Health Initiative, there is growing debate over the effects of estrogen and the risk of cardiovascular disease and stroke. While women aged 30 to 50 have about five times less risk of stroke than men, this difference disappears when women reach menopause. Research studies show that estrogen protects animals from experimental stroke, but recent clinical trials with certain hormone replacement therapies in older women did not show protection from stroke.

Study results appear on the online version of Molecular Pharmacology. Chris Stirone, Sue P. Duckles and Diana N. Krause of the UCI Department of Pharmacology assisted with the study. The National Institutes of Health provided support.

Mitochondria are the power plants of cells responsible for burning the calories in our diet with the oxygen that we breathe to generate carbon dioxide, water and the energy for our cells. The cellular energy is used for two purposes, to generate heat to maintain our body temperature and to synthesize ATP (adenosine triphosphate), a chemical form of energy which permits us to do work such as exercise, think, write, and make and repair cells and tissues.

When the mitochondria burn our dietary fuel, they also generate a toxic by-product called oxygen radicals, the mitochondrial equivalent to the smoke generated by coal-burning power plants. Oxygen radicals, in turn, damage the mitochondria and the surrounding cell. When sufficient oxidative damage accumulates in the mitochondria and the cell, the cell dies. Hence, the chronic level of mitochondrial oxidative stress is believed to help determine an individuals aging rate and susceptibility to a variety of diseases such as cardiovascular disease, stroke, diabetes, memory loss, forms of deafness and vision loss.